There are currently more than 1.7 million persons living in the United States with an amputation (not including finger amputations), a large fraction of whom are upper extremity amputees (over 500,000) (Ziegler-Graham et al., 2008). Hand, trans-radial or trans-humeral amputations cause dramatic loss of an amputee's ability to perform everyday upper extremity tasks. Currently many prosthetic arm users are dissatisfied with available prostheses as 20-45% amputees do not wear body-powered and electric prostheses and prefer to use non- prehensile prostheses as cosmetic devices (Datta et al., 2004; Biddiss & Chau, 2007a; Biddiss & Chau, 2007). We propose to develop a bold and innovative prosthetic device, which is directly attached to residual bone and muscles and allows simple prosthetic control (Farrell & Prilutsky, 2011). This device combines the ideas of bone anchored prostheses with an innovative method of harnessing residual muscles and tendons in the amputated limb to allow them to actuate and sense the external prosthesis with multiple degrees of freedom. This device operates by transmitting force developed by residual muscles via alloplastic tendons passing through the skin and bone integrated implant to the external prosthesis. The central element of the device is the implant with tendon tubes, which allow for frictionless transmission of muscle force and maintenance of skin integrity preventing skin stretch and infiltration of bacteria. The project is a proof-of-concept study with the general goal to develop a prosthetic device that is directly attached to the residual limb and controlled and sensed by the residual muscles. In Specific Aim 1, we plan to develop and refine an implant design for a muscle actuated prosthesis in a rat model. We will implant a group of rats with bone anchored prosthetic foot which is actuated by one ankle extensor and one ankle flexor through connectors sealed inside the residuum. At least two methods of muscle attachments to the artificial foot will be tested: (1) an accordion-like attachment and (2) an elastic tube attachment. In Specific Aim 2, we will evaluate the limits of neuromuscular plasticity that are required to control prosthetic devices by residual muscles. To test the extent to which neuromuscular plasticity can modify activation patterns of the residual muscles after prosthetic device implantation, the residual muscles will be implanted with EMG electrodes and sonomicrometry crystals to measure muscle activity and fascicle length changes in two groups of rats. One group of rats will have the residual muscles to perform their natural functions, i.e. flex or extend the ankle. The function of the residual muscles of the second group will be reversed (similar to tendon transfer) so that the flexor will have an extension action at the joint and the extensor, a flexion action. These studies will provide important information about the design features of the proposed prosthetic device and the plasticity of the neuromuscular system and offer solutions to enhance the device functionality and durability.